Zalutumumab significantly improved progression-free survival (PFS) and disease control (response plus stable disease) compared with best supportive care in patients with advanced squamous cell carcinoma of the head and neck in whom standard platinum-based chemotherapy had failed.¹ The investigational drug improved overall survival (OS) compared with best supportive care, but the difference was not statistically significant.

"ZALUTE is the first controlled study to show an EGFR antibody induces clinically meaningful improvement in progression-free survival," said lead author Jean-Pascal Machiels, MD, PhD, of Cliniques Universitaires Saint-Luc-Université Catholique de Louvain, Belgium, at the 2010 ASCO Annual Meeting.

Zalutumumab, a fully humanized, high affinity monoclonal antibody targeted to epidermal growth factor receptor (EGFR), is under development by Genmab in Denmark. The drug has been awarded Fast Track status by the FDA for head and neck cancer patients in whom standard therapies have previously failed.

Study Details

The open-label, parallel-group, phase III ZALUTE trial randomly assigned 286 patients with SCCHN to receive best supportive care plus the option to use methotrexate (n = 95) vs zalutumumab plus best supportive care and no methotrexate (n = 191). Imaging was performed every 8 weeks for assessment of treatment response.

Baseline characteristics were well balanced between treatment arms. Mean age was about 57 (range, 28-80). About 88% were males, and about 82% had an ECOG performance status of 0. Median duration of squamous cell carcinoma of the head and neck was about 19 weeks at entry to the trial. About two-thirds had distant metastasis. About 40% received prior radiation, and about 55% underwent surgery. About 40% had concurrent chemoradiation therapy, 16% had induction chemotherapy, and 83% had been treated with palliative chemotherapy.

Dr. Machiels explained that zalutumumab was titrated to grade 2 rash to obtain maximal efficacy (as rash is associated with efficacy). The monoclonal antibody was given once a week, and patients were treated until disease progression. The dose was increased by 4 mg/kg every 2 weeks until the appearance of rash.

Zalutumumab did not significantly improve OS: Median OS was 5.2 months for the control arm vs 6.7 months in the zalutumumab arm. Six-month OS was 42% in the control arm vs 57% in the zalutumumab arm. PFS was significantly better in the zalutumumab arm (P = .0010). Median PFS was 8.4 weeks vs 9.9 weeks, respectively. The 26-week PFS was 7.3% in the control arm vs 20% in the zalutumumab arm.

PFS was consistently improved by zalutumumab in all subgroups, including age, sex, performance status, location of primary tumor, distant metastasis, duration of disease, and EGFR expression. Disease control was achieved in 48% vs 72%, respectively.

Adverse events (all grades) more frequently occurring with the monoclonal antibody included skin rash (92% vs 0% in the control arm), anemia (25% vs 19%), pyrexia (22% vs 13%), headache (17% vs 6%), weight loss (16% vs 9%), diarrhea (13% vs 4%), and hypomagnesemia (12% vs 2%). ■

Reference

1. Machiels J-P, Subramanian S, Ruzsa A, et al: An open-label, randomized, phase III trial of zalutumumab, a human monoclonal EGF receptor antibody, versus best supportive care, in patients with noncurable squamous cell carcinoma (SCCHN) of the head and neck who have failed platinum-based chemotherapy (ZALUTE). 2010 ASCO Annual Meeting. Abstract LBA5506. Presented June 7, 2010.